Insulin Resistance Medical Author: Ruchi Mathur, M.D.
Medical Editor: Jay W. Marks, M.D.
What is insulin resistance?
Insulin is a hormone that is produced by the Islets of Langerhans , small groups of cells that are scattered throughout the pancreas . The insulin is released into the blood and travels to all parts of the body. Insulin is an important hormone that has many actions within the body. Most of the actions of insulin are directed at metabolism (control) of carbohydrates (sugars and starches), lipids (fats), and proteins . Insulin also is important in regulating the cells of the body including their growth.
Insulin resistance (IR) is a condition in which the cells of the body become resistant to the effects of insulin, that is, the normal response to a given amount of insulin is reduced. As a result, higher levels of insulin are needed in order for insulin to have its effects.
What causes insulin resistance?
There are probably several causes of IR. It tends to occur in older individuals and in individuals who are obese. There probably is a strong genetic factor (an inherited component), and some medications also can lead to IR. IR may be preceded by gestational diabetes (diabetes that develops transiently during pregnancy).
What is the relationship between insulin resistance and diabetes?
Type 2 diabetes is the type of diabetes that occurs later in life. IR precedes the development of type 2 diabetes, sometimes by years. In individuals who will ultimately develop type 2 diabetes, it is believed that blood glucose and insulin levels are normal for many years; then at some point in time, IR develops.
One of the actions of insulin is to cause the cells of the body, particularly the muscle and fat cells, to remove and use glucose from the blood. This is one way in which insulin controls the level of glucose in blood. Insulin affects the cells by binding to insulin receptors on the surface of the cells. You can think of it as insulin "knocking" on the doors of muscle and fat cells. The cells hear the knock, open up, and let glucose in to be used by the cell. With IR, the muscles don't hear the knock as well (they are resistant), and the pancreas is notified that it needs to make more insulin, which increases the level of insulin in the blood and causes a louder knock.
The resistance of the cells continues to increase over time. As long as the pancreas is able to produce enough insulin to overcome this resistance, blood glucose levels remain normal. When the pancreas can no longer produce enough insulin, the blood glucose levels begin to rise, initially after meals, and eventually in the fasting state too. At this point, type 2 diabetes is present.
What medical conditions are associated with insulin resistance?
Several medical conditions are associated with IR. It may be that IR is the cause of some of these conditions, but this has not yet been proven. Associated conditions include:
Fatty liver: Fatty liver is strongly associated with IR. The accumulation of fat in the liver is a manifestation of the disordered control of lipids that occurs with IR. Fatty liver associated with IR may be mild or severe. Newer evidence suggests that fatty liver may even lead to cirrhosis of the liver. For more, please read the Fatty Liver article.
Arteriosclerosis: Arteriosclerosis is a process of progressive thickening and hardening of the walls of medium-sized and large arteries. Arteriosclerosis is responsible for coronary artery disease ( angina and heart attacks ) and strokes. Other risk factors for arteriosclerosis include high levels of "bad" ( LDL ) cholesterol , high blood pressure , smoking, diabetes, and a family history of arteriosclerosis. For more, please read the Heart Attack Prevention article.
High blood pressure: High blood pressure (hypertension), as previously discussed, is a risk factor for both coronary artery disease and stroke . High blood pressure can be managed with a combination of diet, exercise, medication, and weight loss. For more, please read the High Blood Pressure article.
High blood cholesterol: Elevated levels of cholesterol, particularly bad or LDL cholesterol , as previously discussed, is a risk factor for coronary artery disease and strokes. Like high blood pressure, the levels of cholesterol usually can be controlled with a combination of diet, exercise, medication, and weight loss. For more, please read the Cholesterol and Your Heart article.
Polycystic ovarian disease: Polycystic ovarian disease is a hormonal problem that affects young women. It is associated with irregular periods or no periods at all, obesity , and increased growth of body hair. For more, please read the Polycystic Ovarian Disease article.
Acanthosis nigricans : Acanthosis nigricans is a cosmetic condition strongly associated with IR in which there is darkening of the skin in areas where there are creases such as the neck and arm pits.
Who is at risk for insulin resistance?
Individuals are more likely to have or develop IR if they: - are overweight with a body mass index (BMI) more than 25,
- are a man with a waist more than 40 inches or a woman with a waist more than 35 inches,
- are over 40 years of age (sorry, but true!),
- are Latino, African American, Native American or Asian American,
- have close family members with type 2 diabetes, high blood pressure or arteriosclerosis,
- have had gestational diabetes,
- have high blood pressure, high blood triglycerides , low HDL cholesterol or arteriosclerosis,
- have polycystic ovarian disease,
- have acanthosis nigricans.
How is insulin resistance diagnosed?
A physician can identify individuals who are likely to have IR with a detailed patient history, patient physical examination, and laboratory testing utilizing the risk factors listed in the previous section.
The simplest way to make the diagnosis of IR is by looking at blood glucose levels. The fasting blood glucose level usually is used to make a diagnosis of diabetes; however, with IR, a better measurement is the blood glucose level two hours after drinking 75 grams of glucose. If blood glucose levels are greater than 140 mg/dl two hours after drinking the glucose, IR probably is present. The reason that the two-hour level is better than the fasting level for diagnosing IR is that the two-hour measurement will become abnormal before the fasting level. If fasting blood sugar levels are used, however, values above 110 mg/dl suggest IR. Some groups have recommended that a fasting level greater than 95 mg/dl be used to suggest the presence of IR.
There are more sophisticated tests for the diagnosis or confirmation of IR; however, they are expensive or complicated and are not necessary for managing patients. These tests are used primarily for research purposes.
How is insulin resistance managed?
Insulin resistance can be managed in two ways. First, the need for insulin can be reduced, and second, the sensitivity of cells to the action of insulin can be increased.
Life-style changes: The need for insulin can be reduced by altering the diet, particularly the carbohydrates in the diet. Carbohydrates are absorbed into the body after they are broken up into their component sugars. Some carbohydrates are broken up and absorbed faster than others and are referred to as having a high glycemic index . These carbohydrates increase the blood glucose level more rapidly and require the secretion of more insulin to control the level of glucose in the blood. Examples of carbohydrates with a high glycemic index that rapidly raise blood glucose levels include unrefined sugars, white breads and unrefined corn products (for example, bagels, mashed potatoes, doughnuts, corn chips, and french fries). Examples of foods with a low glycemic index include those with higher fiber content such as whole grain breads and brown rice. Non-starchy vegetables are another example of foods with a low glycemic index (for example, broccoli, green beans, asparagus, carrots, and greens).
Several studies have shown that weight loss and aerobic exercise (without weight loss) increases the rate at which glucose in the blood is taken up by muscle cells as a result of improved sensitivity to insulin.
There are two important studies that have looked at the prevention of type 2 diabetes. Both studies took patients who could not control their blood glucose levels, which, for the purposes of this discussion, can be considered the same as IR. One study done in Finland, showed that changes in diet and exercise reduced the development of diabetes by 58%. Another study, done in the United States and referred to as the DPP study, showed a similar reduction in diabetes with diet and exercise.
Medications: Metformin (Glucophage) is a medication that is used for treating diabetes. It has two mechanisms of action that help to control blood glucose levels. It prevents the liver from releasing glucose into the blood, and it increases the sensitivity of muscle and fat cells to insulin so that they remove more glucose from the blood. Because of these actions, metformin reduces blood insulin levels. The DPP studied the effects of metformin in addition to diet and exercise on the prevention of diabetes in IR. Metformin reduced the development of diabetes by 31%. (Note, however, that the benefit was not as great as diet and exercise!) Metformin is a reasonable safe medication when used in the right population. Although there are gastrointestinal side effects with metformin, it usually is well-tolerated.
Another study, the STOP NIDDM (Study to Prevent non insulin dependent diabetes) trial, studied individuals with IR by treating them with a medication called acarbose (Precose). Acarbose works in the intestines to slow the absorption of sugars, and this effect would reduce the need for insulin after meals. The study found that acarbose reduced the development of diabetes by 25%.
Other medications in a class of drugs called thiazolidinediones, e.g., pioglitazone (Actos), rosiglitazone (Avandia), also increase sensitivity to insulin. At this time, however, these medications are not routinely used, in part because of liver toxicity that requires monitoring of blood liver tests.
One study, the TRIPOD (Troglitazone in Prevention of Diabetes) study, treated patients with gestational diabetes, a precursor of IR and diabetes, with troglitazone (Rezulin), however, because of severe toxic liver effects, troglitazone has been taken off the market and is no longer available. Among the women treated with troglitazone, diabetes was prevented in 25%.
What's new in insulin resistance?
It is only in recent years that IR has been gaining importance as a disease in its own right. It now appears that intervention can delay the onset of overt diabetes. Future longer-term studies will need to determine whether treatment can prevent the development of diabetes and its complications.
Lifestyle changes (e.g., diet, exercise) clearly are important in delaying the development of diabetes in individuals with IR, and education about these changes needs to be directed to groups at risk for diabetes. Childhood obesity is on the rise in the United States as well as other countries, and changes need to be made in school cafeterias and in the food choices offered to children and teens at home.
The value of diet, exercise and medication in combination needs to be evaluated to determine if the combination is better than only diet and exercise. - Insulin resistance is a condition in which the cells of the body become resistant to the hormone, insulin.
- Insulin resistance precedes the development of type 2 diabetes.
- Insulin resistance is associated with other medical conditions including fatty liver, arteriosclerosis, high blood pressure, elevated blood cholesterol, polycystic ovarian disease, and acanthosis nigricans.
- Individuals are more likely to have insulin resistance if they have any of the associated medical conditions listed above. They also are more likely to be insulin resistant if they are obese or are Latino, African-American, Native American, and Asian-American.
- Insulin resistance is diagnosed primarily on the basis of blood sugar (glucose) levels.
- Insulin resistance can be managed with diet, exercise, and medication.
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